Current treatments for smoking cessation fail most of the time, and robust new treatments, including medications, are sorely needed. Because ofthe substantial costs and time involved in clinical trials, medications subjected to these trials must be those with the greatest promise of success. The purpose of medication screening studies is to quickly and cheaply evaluate the clinical potential of medications, so that promising drugs proceed to clinical trials and unpromising drugs do not. However, there is no human screening procedure for medications in which results are clearly predictive of smoking cessation outcome in clinical trials with those medications. This proposal aims to improve procedures for human screening of potential medications for smoking cessation prior to clinical trials of the efficacy of those medications. Logically, studies on human screening of cessation medications should simulate, within practical limitations, clinical trial procedures. Thus, emphasis should be placed on smoking abstinence as the primary index of medication response, as there are no other clear short-term predictors of long-term abstinence. We will examine sensitivity to medication effects as a function of two methods used to increase the motivation and likelihood of abstinence in smokers participating in a short-term screening study: 1) ?natural? motivation due to treatment seeking status of participants, and 2) ?artificially supported? motivation using monetary incentives contingent on smoking abstinence. We will assess 160 treatment-seeking smokers and 160 non-treatment seeking smokers, half of whom will receive monetary reinforcement on a daily basis contingent on being abstinent (verified by expired-air Co <= 8 ppm) and half of whom will not receive reinforcement far abstinence. In these groups, we will compare effects of 5 days? exposure to 21 mg nicotine versus placebo patch, using a within-subjects cross-over design. Our main dependent measures will be days of smoking abstinence and continuous 5-day abstinence (dichotomous outcome), with cigarettes/day, craving, withdrawal, negative affect, and ADHD symptoms as secondary measures. We hypothesize that differences between nicotine vs placebo patch will be greater in treatment seekers than non-seekers, and in those receiving abstinence reinforcement vs no reinforcement. Secondarily, we will examine changes in the magnitude of nicotine effects as a function ofthe duration of exposure to medication across days within the 5-day treatment period, to identify the point of peak early medication effects. Assessment of self-report measures will be conducted in the natural environment, as well as the lab, to determine the influence of method of assessment on medication response. We will also examine individual differences in nicotine responses. Results will provide immediate directions for improving screening evaluations of cessation medications. Future directions include testing the utility of this improved screening procedure with novel medications, the long-range objective. This research will ultimately help us better understand how to more quickly and efficiently evaluate potential medications for smoking cessation, a goal with very high public health significance.